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81.
Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis 总被引:5,自引:0,他引:5 下载免费PDF全文
Taranta A Migliaccio S Recchia I Caniglia M Luciani M De Rossi G Dionisi-Vici C Pinto RM Francalanci P Boldrini R Lanino E Dini G Morreale G Ralston SH Villa A Vezzoni P Del Principe D Cassiani F Palumbo G Teti A 《The American journal of pathology》2003,162(1):57-68
Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity. 相似文献
82.
Ricca V Nacmias B Boldrini M Cellini E di Bernardo M Ravaldi C Tedde A Bagnoli S Placidi GF Rotella CM Sorbi S 《Neuroscience letters》2004,365(2):92-96
Various studies have evaluated the possible role of the -1438G/A polymorphism within the 5-HT2A receptor gene in the susceptibility to Eating Disorders (EDs). One hundred and forty-eight ED patients (EDp) and 89 control subjects were interviewed by means of the Eating Disorder Examination (EDE) and analyzed for distribution of the -1438G/A polymorphism. Patients with the AA genotype suffering from Anorexia Nervosa and Bulimia Nervosa showed higher Weight and Shape Concern (P = 0.003 and P = 0.010, respectively) scores and greater overall severity of the ED psychopathology (EDE total score) (P = 0.012). The obtained preliminary data suggest the use of dimensional psychopathological measures in ED genetic studies. 相似文献
83.
Ultrastructural Localization of Alpha-Naphthyl Acid Esterase in Human TM Lymphocytes 总被引:2,自引:0,他引:2 下载免费PDF全文
Antonio Zicca Annaldo Leprini Angela Cadoni Adriano T. Franzi Manlis Ferrarini Carlo E. Grossi 《The American journal of pathology》1981,105(1):40-46
The localization of alpha-naphthyl acid esterase (ANAE) activity in T lymphocytes with receptors for IgM (TM cells) have been studied at the electron microscope. The electron-opaque product of the cytochemical reaction was detected around, but never inside, single (or groups of) vesicles, which suggested a possible membrane localization of the enzyme activity. These same vesicles were found to contain acid phosphatase by both light- and electron-microscopic examination and were bound by unit membranes; this data indicates that they likely represent primary lysosomes. The presence of such lysosomes in a restricted paranuclear area is a distinctive feature of TM cells. 相似文献
84.
Sala G Galimberti G Canevari C Raggi ME Isella V Facheris M Appollonio I Ferrarese C 《Neurobiology of aging》2003,24(7):909-914
Various studies suggested that inflammation is involved in the pathogenesis of Alzheimer's disease (AD). We investigated cytokine release from LPS-stimulated blood cells of 32 AD patients, with different disease severity, compared to 16 age-related controls. A significant decrease of IL-1beta and IL-6 secretion was observed in severely demented patients; TNF-alpha release was also decreased, but not significantly. By contrast, mild and moderate patients showed a cytokine release similar to controls. IL-1beta, IL-6 and TNF-alpha secretion was negatively correlated with the severity of dementia, quantified by the MMSE. Our data suggest that alterations of the immune profile are associated with AD progression. 相似文献
85.
86.
Moss RB Giermakowska WK Diveley JP Savary JR Wallace MR Maigetter RZ Jensen FC Carlo DJ 《Journal of human virology》2000,3(1):44-49
BACKGROUND: The chemokine receptors CXCR4 and CCR5 have been identified as the major coreceptors for HIV-1 on CD4+ cells and macrophages. The natural ligands for these receptors are SDF-1 and the beta-chemokines (MIP-1alpha, MIP-1beta, RANTES), respectively, and are the products of a variety of immune cells, including CD8+ T lymphocytes. STUDY DESIGN/METHODS: We hypothesized that the ability to stimulate the natural ligands for these receptors using an immune based therapy might influence in vivo chemokine receptor expression. RESULTS: In vivo CXCR4 expression remained stable after treatment with an HIV-1 Immunogen (REMUNE), whereas CCR5 expression on CD4+ T cells decreased (p < .05). Furthermore, HIV-1 antigen-specific production of beta-chemokines in vitro was also augmented (P < .05). CONCLUSIONS: These preliminary results suggest that this HIV-1-specific immune-based therapy can stimulate antigen-specific beta-chemokine production in vitro and downregulate CCR5 receptor expression on CD4 cells in vivo. 相似文献
87.
Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia 总被引:1,自引:0,他引:1
Matthew G. Guenther Lee N. Lawton Tatiana Rozovskaia Garrett M. Frampton Stuart S. Levine Thomas L. Volkert Carlo M. Croce Tatsuya Nakamura Eli Canaani Richard A. Young 《Genes & development》2008,22(24):3403-3408
Mixed-lineage leukemia (MLL) fusion proteins are potent inducers of leukemia, but how these proteins generate aberrant gene expression programs is poorly understood. Here we show that the MLL-AF4 fusion protein occupies developmental regulatory genes important for hematopoietic stem cell identity and self-renewal in human leukemia cells. These MLL-AF4-bound regions have grossly altered chromatin structure, with histone modifications catalyzed by trithorax group proteins and DOT1 extending across large domains. Our results define direct targets of the MLL fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in cancer. 相似文献
88.
Carlo M. Pesce Rosanna Colacino 《Virchows Archiv : an international journal of pathology》1987,412(2):151-154
Summary The volume of the adenomatous mucosa (V), the area of the surface epithelium (Ss), the area of the glandular epithelium (Sg), and theSg:Ss ratio were calculated in a series of 14 adenomatous polyps (APs) of a case of multiple polyposis of the colon. The equation of simple allometry was used to study the relative growth of the four series of values.Ss grew isometrically with size;Sg overgrewSs and accounted for most of the increase inV. TheSg:Ss ratio increased withSg andV. 相似文献
89.
Nappi C Di Spiezio Sardo A Guerra G Di Carlo C Bifulco G Acunzo G Sammartino A Galli V 《Menopause (New York, N.Y.)》2004,11(4):447-455
OBJECTIVE: To compare nasal symptomatology and function and local concentrations of estradiol (E2), estradiol receptor (ERalpha), vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) in nasal biopsies of 20 postmenopausal women complaining of paradoxical nasal stuffiness before and after treatment with intranasal or transdermal E2. DESIGN: Twenty healthy postmenopausal women willing to start hormone therapy (HT) were allocated to one of two groups, using a computer-generated randomization list.Ten postmenopausal women were treated with transdermal 17beta-estradiol 50 microg daily plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group A). Ten postmenopausal women were treated with intranasal 17beta-estradiol 300 microg/day (one spray delivery of 150 microg per nostril) plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group B). Fourteen fertile women undergoing nasal mucosa biopsy during plastic surgery were used as controls for the immunohistochemical evaluation (Group C).All women in groups A and B underwent evaluation of nasal stuffiness score, mucociliary transport time, rhinoscopy, and active anterior rhinomanometry at the beginning of the study and after, VIP, SP, and 6 months of HT. Nasal biopsies and evaluation of local concentrations of E2, ERalpha NPY were performed in groups A and B before and after 6 months of HT and in group C. RESULTS: Both intranasal and transdermal HT improve nasal symptomatology and nasal mucosa appearance and reduce mean mucociliary transport time. The effectiveness of intranasally administered therapy at improving nasal function is significantly better than transdermal therapy. In comparison with premenopausal controls, untreated postmenopausal women of group A and B showed significantly decreased immunopositivity for E2, ERalpha, and SP. HT induced a significant increase in E2, ERalpha, VIP, and SP and a decrease in NPY immunopositivity. Intranasal therapy was associated with a significantly higher immunopositivity for VIP and SP. CONCLUSIONS: HT improves nasal function and symptomatology in postmenopausal women with paradoxical nasal stuffiness, modulating nasal mucosa function through an action on cholinergic, adrenergic, and sensory peptides. Intranasally administered HT is more effective at improving nasal function than transdermal HT. 相似文献
90.
Marc Gellman Susan Spitzer Gail Ironson Maria Llabre Patrice Saab Rosemary De Carlo Pasin Donald J. Weidler Neil Schneiderman 《Psychophysiology》1990,27(5):544-551
Ambulatory blood pressure was studied as a function of posture, place, and mood in 131 subjects classified according to race, gender, and hypertensive status. The effect of posture was significant and explained a substantial proportion of within-subject variability. After controlling for posture, significant place and mood effects were observed when subjects were sitting but not when they were standing. Home vs. work differences in both systolic and diastolic blood pressure were significantly greater in Whites than in Blacks. Similar differences in systolic blood pressure were greater in mild hypertensive than in normotensive subjects. The results of this study underscore the need to control for effects of posture when interpreting ambulatory blood pressure readings. 相似文献